1. Field of the Invention
This invention concerns an in situ method for repair of meniscal injuries. In particular, the invention concerns a minimally invasive method for repair of meniscal injuries comprising induction of meniscal regeneration in situ by introducing an adhesive collagen-polyethylene glycol (PEG) hydrogel to a site of injury. The collagen-PEG hydrogels strongly bind the torn region of the meniscus for a period of time needed for healing and promote cell migration and extracellular matrix formation in the torn zone.
2. Background and Related Disclosures
Repair of meniscal injuries is one of the most common operative procedures utilized in orthopedics surgery today (Koski J A, Ibarra C, Rodeo S A, Warren R F: Meniscal Injury and Repair-Clinical Status. Tissue Engr. Orthop. Surg., 31(3) :419-435 (2000)).
Meniscal tears are common in young individuals, usually as a result of sports-related activities, as well as in older population suffering from degenerative joint diseases. The meniscus plays an important role in load transmission, shock absorption and knee joint stability. Injuries to the meniscus cause pain, disability and damage to the articular cartilage on the femoral and tibial surfaces, leading to development of degenerative changes and osteoarthritis.
Early treatments for meniscal injuries typically consists of partial or total meniscectomy. This approach frequently results in accelerated cartilage degeneration due to decreased joint contact area and the resultant rise in contact stress. Removal of only 15-34% of the meniscus can produce a 350% increase in contact stress (Seedhon B, Hargreaves, D: Transmission of the load in the knee joint with special references to the role of the menisci: II. Experimental results, discussion, and conclusions. Engineering in Med., 8:220 (1979)). Therefore, preservation of meniscal tissue and successful lesion repair are the goals of most current treatment methods for meniscal injury.
Currently, a meniscal transplantation is one of the available treatment options for patients whose injury, such as a meniscal tear, is severe and complex. Fresh-frozen allograft menisci have been shown to successfully attach and heal to the recipient periphery in experimental models. Studies have also shown evidence of repopulation of the allograft with host-derived cells. The clinical studies show that 71% of meniscal transplants result in complete healing at 8 months post operation. Despite these positive results, issues with availability of allograft tissue, tissue rejection, disease transmission and a lack of long-term data have limited the use of this approach.
The ability of a meniscal lesion to heal, either spontaneously or after surgical repair, is influenced by the proximity of the tear to the limited vascular supply, the size and complexity of the tear, and the presence of concurrent ligamentous instability. Lesions located in the peripheral 10-25% of the meniscus, in so called red zone where vascularity is greatest, have the greatest chance for successful repair. Lesions in the remaining avascular region of the meniscus, so called white zone, have shown only limited capacity, if at all, for repair and healing.
Recognizing the importance of the formation of a fibrin clot to the healing process, several researchers have used an autologous clot to enhance repair of avascular meniscal lesions. Using a canine model with stable 2 mm diameter defects filled with a fresh blood clot, fibrous reparative tissue was observed to fill in the defect site. The clot was thought to provide a scaffold for cell migration and proliferation, as well as chemotactic and mitogenic stimuli such as platelet-derived growth factor and fibronectin. However, in these studies, the histological appearance of the reparative tissue was notably significantly different from normal meniscus. Furthermore, cells migrating into the clot did not appear to synthesize a significant amount of extracellular matrix (Amer. J. Sports Med., 17:393-400 (1989). Consequently, the reported clinical results performed with autologous clots do not have a very positive outcome.
Moving toward a regenerative approach, more recent studies have been directed at developing a resorbable porous collagen scaffold to replace the injured portion of the meniscus when repair is not possible. These scaffolds provide a substrate for migration and repopulation by native cells. See, for example, U.S. application Ser. Nos. 10/626,459, 10/104,677, 10/625,822, 10/625,245 and 10/882,581, by inventors, all hereby incorporated by reference.
Using a canine partial meniscectomy model and an appropriately shaped collagen implant, Stone and co-workers demonstrated that 63% of the implants showed evidence of substantial meniscal regeneration at 12 months (Stone K R, Rodkey W G, Weber R J, Meniscal regeneration with copolymeric collagen scaffolds: In vitro and in vivo studies evaluated clinically, histologically, and biochemically Am. J. Sports Med., 20:104-111 (1992)). In these studies, histologically, the repair tissue seemed similar to normal canine meniscus. The limited clinical results for this approach indicated that regeneration of some meniscus-like tissue could be possible for patients with severe meniscal injuries who would have otherwise have to undergo partial or total meniscectomies.
The studies, described in the above cited patent applications, have shown that through the use of a fibrin clot or other appropriate scaffold material, replacement fibrocartilage can form through cellular integration, proliferation and tissue ingrowth. The regenerative treatment approach provides an appropriate follow-up to meniscectomy, potentially preventing cartilage degradation while restoring the function of the joint. Many meniscal tears in the avascular region are initially small and cause minor discomfort to the patient and, consequently, a significant number of the meniscal tears are left untreated due to the lack of fast, reliable arthroscopic repair techniques which would preserve the functional integrity of the meniscus. Over time, the size of these meniscal tears grows and cause significant cartilage damage, as well as pain and loss of joint mobility.
To overcome the above stated problems, the current invention provides a minimally invasive method for repair of meniscal tear in situ utilizing an arthroscopic procedure to introduce at the site of the meniscal injury an adhesive collagen-PEG hydrogel, preferably supplemented with a source of intra-articular fibroblastic cells or with a support matrix which guides repair of the meniscal tear. Thus, the current invention provides an alternative conservative treatment to a partial meniscectomy.
All patents, patent applications and publication cited herein are hereby incorporated by reference.